Rivaroxaban, having a chemical name of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl-2-thiophenecarboxamide, has a structural formula (I) as follows:

Rivaroxaban is a novel highly selective anticoagulant developed by Bayer Company, Germany. Rivaroxaban was approved for marketing by the European Union in September 2008, and the brand name is Xarelto. Rivaroxaban can competitively inhibit the activity of free and bound factor Xa as well as prothrombin, prolong the prothrombin time (PT) and activated partial thromboplastin time (APTT) in a dose dependent mode, and can be used to prevent the formation of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing hip and knee replacement surgery.
The demand for Rivaroxaban will increase gradually along with its clinical application. WO 2005068456 disclosed a method for synthesizing Rivaroxaban, involving an important intermediate shown by formula 4, i.e., compound 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one. The final product Rivaroxaban can be obtained by reacting the intermediate compound 4 with 5-chlorothiophene-2-carbonyl chloride in last step.

Compound 4 is an important intermediate for synthesizing Rivaroxaban. WO 0147919 also disclosed a method for preparing Rivaroxaban by using compounds 2-[(2S)-2-oxiranyl-methyl]-1-H-isoindole-1,3(2H)-dione and 4-(4-aminophenyl)-3-morpholinone as starting materials, in which the intermediate compound 4 is also involved, and the synthesis scheme is showed as follows:

The major problems of this method are that:
1) the raw material 2-[(2S)-2-oxiranyl-methyl]-1-H-isoindole-1,3(2H)-dione is expensive; and the amino on oxazolidinone ring of Rivaroxaban is protected by phthalimide. Thus the removal of the protective group with methylamine increases the reaction steps and cost;
2) the reaction needs high temperature, long reaction time, high energy consumption, and high-cost, thus the process is not suitable for industrial production.
Therefore, the popularization and application of Rivaroxaban certainly will be promoted, if the preparation process of its intermediate compound 4 is optimized to decrease the price of drug substance.